chr14-92555860-A-G

Position:

• chr14-92555860-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024832.5(RIN3):​c.154A>G​(p.Ile52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIN3 NM_024832.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.461

Genes affected

RIN3 (HGNC:18751): (Ras and Rab interactor 3) Summary: This protein encoded by this gene is a member of the RIN family of Ras interaction-interference proteins, which are binding partners to the RAB5 small GTPases. The protein functions as a guanine nucleotide exchange for RAB5B and RAB31. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029156446).
• BP6: Variant 14-92555860-A-G is Benign according to our data. Variant chr14-92555860-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2478176.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIN3	NM_024832.5	c.154A>G	p.Ile52Val	missense_variant	2/10	ENST00000216487.12	NP_079108.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12	c.154A>G	p.Ile52Val	missense_variant	2/10	1	NM_024832.5	ENSP00000216487	P2
RIN3	ENST00000555589.5	c.154A>G	p.Ile52Val	missense_variant, NMD_transcript_variant	2/9	1		ENSP00000450682
RIN3	ENST00000620541.4	c.154A>G	p.Ile52Val	missense_variant	2/11	5		ENSP00000480603	A2
RIN3	ENST00000556385.5	n.21A>G		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.41
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.91	N;.
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.080	N;.
REVEL	Benign	0.0090
Sift	Benign	0.95	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.21		Gain of MoRF binding (P = 0.0917);Gain of MoRF binding (P = 0.0917);
MVP		0.14
MPC		0.22
ClinPred		0.040	T
GERP RS		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.012
gMVP		0.089

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-93022205;